I Like to Draw Pictures of Random Molecules

[sekio]

That's page 151, not 161

here is the article

 

[Anon0631]

Here's another one. If the n,n-diethyl substitution of LSD can be cyclicised to form LSZ - a substance with very similar properties, then can the same logic be applied to DET?

Or DMT?

 

[sekio]

The latter compound is N-methylenetryptimine. Would decompose to tryptamine and formaldehyde.

I think cyclic analogues of DET have been made (pyr-T, pip-T) but they are generally regarded as fucked up poisons.

 

[Anon0631]

It's fun playing this game - well, until someone gets poisoned.

 

[QUARE]

 

[ebola?]

IIRC, pyr-T involved multi-hour blackouts, one of which had the subject walking out onto the street...

ebola

 

[sekio]

QUARE, I don't think you can form S-methoxy thiophenes easily.

 

[QUARE]

I really need to finish that book. lol

Anyway what makes it so hard to form ?

 

[sekio]

they are never observed in chemistry
thiophene-1-oxides have a double bonded oxygen afaik

 

[QUARE]

 

[pharmakos]

tasty

 

[atara]

Surprised this rather promising tree hasn't been barked up a bit more:

Everyone wishes it were. . .

Sadly, the authors keep dying of kidney failure.

 

[bloodshed344]

Surprised this rather promising tree hasn't been barked up a bit more:




Sadly, the authors keep dying of kidney failure.

What's with the allyloxy? and can you think of a ghetto hypothetical name for this, it looks very strange. why not try the amine on the left position instead of where it's at (it's currently at the same spot it'd be on 2C-B-IND but the guys on the last page said the amine would be better to the side)


Obviously I know nothing at all about this.

 

[atara]

Structural rationale: First, allylescaline was the most potent of the mescaline analogs, though cyclobutyl may be somewhat better (and more stable).

Secondly, jimscaline had improved potency relative to mescaline, while 2CB-Ind had reduced potency relative to 2C-B. But TCB-2 had improved potency relative to 2C-B! What can we make of this?

The key, I suggest, lies in the distance between the nitrogen and the upper-methoxy group, if the molecule is oriented so the amine is at the "top". In 2CB-Ind, the indane actually pushes the nitrogen closer to the methoxy, which is unfavorable, but in TCB-2, the cyclobutane pushes it away, which is favorable. But in mescaline, the ortho methoxy has migrated over to the meta position, increasing the nitrogen-oxygen distance more and making the indane restriction favorable! We can capitalize on this by using the optimal 4-substituent.

http://pubs.acs.org/doi/abs/10.1021/jm060272y

Also, thiophene S-oxides are hepatotoxic and should be avoided. BTCP is a prime example.

 

[sekio]

thiophene S-oxides are hepatotoxic and should be avoided

Is it all S-oxides? There are many thiophene drugs; tiagabine, duloxetine, thiambutenes, sulfentanil, etc. and I don't think they're hepatotoxic.

I would not claim that because benzene is carcinogenic that phenylalanine would be too.

 

[atara]

Is it all S-oxides? There are many thiophene drugs; tiagabine, duloxetine, thiambutenes, sulfentanil, etc. and I don't think they're hepatotoxic.

I would not claim that because benzene is carcinogenic that phenylalanine would be too.

Much like epoxides, S-oxides are reactive intermediates, but, in the same way that not all naphthalenes are metabolised to epoxides (cf naproxen), not all benzothiophenes are metabolized to their S-oxides. The 2-substituted benzothiophenes (BTCP) seem to be particularly susceptible to this transformation. The S-oxides react readily with thiols, i.e. glutathione:

http://pubs.acs.org/doi/abs/10.1021/ja00020a089?journalCode=jacsat

Tiagabine is apparently discouraged in patients with poor liver function; its metabolism proceeds to the 5-oxo, a conjugated thioester (???). Tiagabine is used to treat seizures, which in any case are worse than hepatotoxicity. http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1157.1997.tb01734.x/pdf

Duloxetine is oxidised in the naphthyl ring, oxidation of thiophene was not mentioned: http://dmd.aspetjournals.org/content/31/9/1142.full

Some hindered S-oxides may be less reactive, but in general the Michael-type reaction seems like it could deplete bodily glutathione in all but the most potent S-oxide-producing drugs.

I feel like I know where this is going: MPA is metabolised primarily at the amine function, though S-oxides are produced and GSH depletion may be a concern, especially in conjunction with e.g. Valium.

 

[sekio]

Here's where I was kind of going: why isn't etizolam (dosed around 1-10mg) toxic like BTCP (1-10mg) ?

 

[blueberries]

http://imgur.com/YiTR475

I drew this up just to see how vastly you could change an ACH without losing too much activity. I made it in a similar format to Bromadol for potency, ideally that middle benzyl ring would be twisted but com ce com ca. The broken benzyl ring on the amine should also increase potency, or make it somewhat more psychoactive but the methylenedioxy ring on the propyl was just for giggles, I would hope it would decrease potency, so it's not such a dangerous chem as Bromadol. Am I right in thinking the Methoxy bond next to the propylpyrole would change it into a potent DRI/NMDA antag instead of an opiate? The 3 positioned hydroxy however should add a bit of opiate flavour I think. That 2-fluoro would also decrease potency slightly, similar to how the oxy on K/MXE does the same, but with those they're double bonded so I'm not sure. Also I got the impression that it would also add a bit of opiateyness to the compound but I'm not so sure.

Anyway, I am by no means a chemist but the ACH's seem a bit like lego so I would hope this works out. Let me know what you think.

 

[pharmakos]

I drew this up just to see how vastly you could change an ACH without losing too much activity. I made it in a similar format to Bromadol for potency, ideally that middle benzyl ring would be twisted but com ce com ca. The broken benzyl ring on the amine should also increase potency, or make it somewhat more psychoactive but the methylenedioxy ring on the propyl was just for giggles, I would hope it would decrease potency, so it's not such a dangerous chem as Bromadol. Am I right in thinking the Methoxy bond next to the propylpyrole would change it into a potent DRI/NMDA antag instead of an opiate? The 3 positioned hydroxy however should add a bit of opiate flavour I think. That 2-fluoro would also decrease potency slightly, similar to how the oxy on K/MXE does the same, but with those they're double bonded so I'm not sure. Also I got the impression that it would also add a bit of opiateyness to the compound but I'm not so sure.

Anyway, I am by no means a chemist but the ACH's seem a bit like lego so I would hope this works out. Let me know what you think.

i think NMDA activity is greatly reduced with that much bulk on the phenyl ring

bit of a frankenstein molecule you have going on there

 

[atara]

http://imgur.com/YiTR475

You appear to have switched the cyclohexyl and phenyl rings.

Here's where I was kind of going: why isn't etizolam (dosed around 1-10mg) toxic like BTCP (1-10mg) ?

Etizolam is metabolized on the alkyl chain; the thiophene S is highly hindered. Upon searching the only reference to a metabolite of etizolam I found was alpha-hydroxyetizolam. The tricycle in etizolam (triazolo-[1,2-a]azepino-[7,6-b]thiazole?) is so weird it's hard to number, but oxidation happens on the ethyl chain attached to the thiophene ring. Wiki calls this the 4-ethyl. I assume the alcohol is then maybe glucuronidated?

Benzene is toxic for metabolism to the epoxide (oxepin), toluene is less toxic because metabolism is 95% to benzyl alcohol and 5% epoxide, and benzyl alcohol is used in IV preparations because the alcohol is metabolized much more readily than the ring to ultimately hippuric acid.

can you think of a ghetto hypothetical name for this, it looks very strange.

In keeping with jimscaline and tomscaline, the only appropriate name for 4-desmethylallyljimscaline is atarascaline, clearly. 8)